Cyclopropanecarboxaldehyde → N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}-2-methylphenyl)benzamide hydrochloride

HRID 922549Notes

Reaction equation

HRID 922549 reaction equation
[ClH:1].[NH2:2][C@@H:3]1[CH2:5][C@H:4]1[C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[C:8]([CH3:21])[CH:7]=1.C(=O)([O-])O.[Na+].[CH:27]1([CH:30]=O)[CH2:29][CH2:28]1.[BH4-].[Na+]>C1COCC1.CO>[ClH:1].[CH:27]1([CH2:30][NH:2][C@@H:3]2[CH2:5][C@H:4]2[C:6]2[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:20])[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[C:8]([CH3:21])[CH:7]=2)[CH2:29][CH2:28]1

Participants

7

Reactant 4

HCID 123114CyclopropanecarboxaldehydeHCID 516892Sodium Bicarbonate2×HCID 4311764Sodium borohydrideHCID 86729915N-[4-(trans-2-aminocyclopropyl)-2-methylphenyl]benzamide hydrochloride

Product 1

HCID 86729918N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}-2-methylphenyl)benzamide hydrochloride

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0.6000000238418579 °C

Procedure

To a solution of N-[4-(trans-2-aminocyclopropyl)-2-methylphenyl]benzamide hydrochloride (90.1 mg) and sodium hydrogen carbonate (50.0 mg) in THF (1.49 mL)/methanol (1.49 mL) was added cyclopropanecarbaldehyde (0.029 mL). The reaction mixture was stirred at 0.60° C. for 1 hr, and ice-cooled to 0° C. and sodium borohydride (22.51 mg) was added. The mixture was stirred at room temperature overnight, and poured into saturated aqueous sodium hydrogen carbonate solution. The reaction mixture was extracted with ethyl acetate, and the extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) and the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (5 mL), and 4N hydrochloric acid/ethyl acetate solution (0.5 mL) was added. The solvent was evaporated under reduced pressure, and the residue was recrystallized from methanol/diisopropyl to give the title compound (55.9 mg).

Workup

  1. temperatureice-cooled to 0° C.
  2. stirringThe mixture was stirred at room temperature overnight
  3. extractionThe reaction mixture was extracted with ethyl acetate
  4. washthe extract was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)
  8. customthe solvent was evaporated under reduced pressure
  9. dissolutionThe residue was dissolved in ethyl acetate (5 mL)
  10. addition4N hydrochloric acid/ethyl acetate solution (0.5 mL) was added
  11. customThe solvent was evaporated under reduced pressure
  12. customthe residue was recrystallized from methanol/diisopropyl

Sources & evidence

ORD record
ord-38d47165c689496991fc0196937d26e2
Source dataset
uspto-grants-2016_03
Patent number
US09278931B2

Reaction notes

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